Limit size lipid nanoparticles and related methods

Abstract

Limit size lipid nanoparticles, methods for using the lipid nanoparticles, and methods and systems for making limit size lipid nanoparticles.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
       1. A device for producing limit size lipid nanoparticles having a diameter from 10 nm to 50 nm, comprising:
 (a) a first inlet for receiving a first solution comprising a first solvent; 
 (b) a first inlet microchannel in fluid communication with the first inlet to provide a first stream comprising the first solvent; 
 (c) a second inlet for receiving a second solution comprising lipid particle-forming materials in a second solvent; 
 (d) a second inlet microchannel in fluid communication with the second inlet to provide a second stream comprising the lipid particle-forming materials in the second solvent; and 
 (e) a third microchannel for receiving the first and second streams, wherein the third microchannel has a first region adapted for flowing the first and second streams and a second region adapted for mixing the contents of the first and second streams to provide a third stream comprising limit size lipid nanoparticles, 
 wherein the third microchannel is configured to receive the first and second streams at a flow rate ratio greater than 1.0, and wherein the second region is configured to provide a fluid flow rate from 1 ml/min to 40 ml/min. 
 
     
     
       2. The device of  claim 1 , wherein the second region of the third microchannel has a height of 79 microns to 130 microns. 
     
     
       3. The device of  claim 1 , wherein the second region of the third microchannel comprises a micromixer. 
     
     
       4. The device of  claim 1 , wherein the second region of the third microchannel comprises bas-relief structures. 
     
     
       5. The device of  claim 4 , wherein the bas-relief structures comprise a plurality of herringbone bas-relief structures. 
     
     
       6. The device of  claim 1 , wherein the second region of the third microchannel has a principal flow direction and one or more surfaces having at least one groove or protrusion defined therein, the at least one groove or protrusion having an orientation that forms an angle with the principal direction. 
     
     
       7. The device of  claim 1 , wherein the first inlet microchannel and the second inlet microchannel each include at least a portion that has a hydraulic diameter of 20 microns to 300 microns. 
     
     
       8. A method of producing limit size lipid nanoparticles having a diameter from 10 nm to 50 nm, the method comprising:
 flowing a first stream through a first inlet microchannel of a fluidic device, the first stream comprising a first solvent; 
 flowing a second stream through a second inlet microchannel of the fluidic device to provide a second stream comprising lipid particle-forming materials in a second solvent; and 
 flowing the first stream and the second stream through a first region of a third microchannel of the fluidic device, the third microchannel in fluidic communication with the first inlet microchannel and the second inlet microchannel, wherein a flow ratio of the first stream and the second stream is greater than 1.0; 
 mixing the first stream and the second stream in a second region of the third microchannel, the second region in fluidic communication with the first region, wherein a combined flow rate of the first stream and the second stream in the second region is from 1 ml/min to 40 ml/min; and 
 flowing a third stream from the second region, the third stream comprising limit size lipid nanoparticles formed by the mixing of the first stream and the second stream. 
 
     
     
       9. The method of  claim 8 , wherein the second region of the third microchannel has a height of 79 microns to 130 microns. 
     
     
       10. The method of  claim 8 , wherein the second region of the third microchannel comprises a micromixer. 
     
     
       11. The method of  claim 8 , wherein the second region of the third microchannel comprises bas-relief structures. 
     
     
       12. The method of  claim 11 , wherein the bas-relief structures comprise a plurality of herringbone bas-relief structures. 
     
     
       13. The method of  claim 8 , wherein the second region of the third microchannel has a principal flow direction and one or more surfaces having at least one groove or protrusion defined therein, the at least one groove or protrusion having an orientation that forms an angle with the principal direction. 
     
     
       14. The method of  claim 8 , wherein the first inlet microchannel and the second inlet microchannel each include at least a portion that has a hydraulic diameter of 20 microns to 300 microns. 
     
     
       15. A system, comprising:
 a first inlet microchannel configured to receive a first solution and provide a first stream comprising the first solution; 
 a second inlet microchannel configured to receive a second solution and provide a second stream comprising the second solution; 
 a third microchannel configured to receive the first stream and the second stream, wherein the third microchannel has a first region adapted for flowing the first stream and the second stream and a second region adapted for mixing the first stream and the second stream to provide a third stream comprising a mixture of the first solution and the second solution; 
 a first pump configured to provide the first solution to the first inlet microchannel at a first flow rate; and 
 a second pump configured to provide the second solution to the second inlet microchannel at a second flow rate; 
 wherein the ratio of the first flow rate to the second flow rate is greater than 1.0, and wherein the second region is configured to provide a fluid flow rate from 1 ml/min to 40 ml/min. 
 
     
     
       16. The system of  claim 15 , wherein the second region of the third microchannel comprises a micromixer. 
     
     
       17. The system of  claim 15 , wherein the second region of the third microchannel comprises bas-relief structures. 
     
     
       18. The system of  claim 15 , wherein the second region of the third microchannel has a principal flow direction and one or more surfaces having at least one groove or protrusion defined therein, the at least one groove or protrusion having an orientation that forms an angle with the principal direction. 
     
     
       19. The system of  claim 15 , wherein the first inlet microchannel and the second inlet microchannel each include at least a portion that has a hydraulic diameter of 20 microns to 300 microns.